Elucidating the Lipoprotein-Mediated Mechanisms Involved in Dietary Fat Mobilization from the Gut

Dietary fat in the form of triglycerides (TGs) is an important energy store in many animal cells. Because fat (oil) and water don’t mix, elaborate mechanisms have evolved to store TGs in and retrieve TGs from lipid droplets (LDs, the cellular organelle that stores neutral lipids) within the polar cytoplasm. Research in the field of LD dynamics is growing tremendously, and new roles for LDs in lipid translocation at both the cellular and organismal levels are continually being discovered. Due to a growing understanding of the role of LDs in lipid homeostasis, abnormal LD dynamics are increasingly being implicated in human diseases such as obesity, diabetes and cardiovascular disease. Understanding the molecular mechanisms underpinning the complex processes of lipid translocation and LD dynamics will not only shed light on the cellular functions of LDs but also provide invaluable insights for designing targeted therapies to combat associated metabolic diseases. The data presented in this thesis establish critical spatial parameters governing lipid translocation: 1) the uptake of fatty acids (FAs) from the lumen of the gut and their storage as TGs in the form of LDs at the apical domain of the enterocyte, and 2) the subsequent incorporation of LD-derived FAs into lipoprotein particles that are eventually carried by the circulation to cells throughout the body.